Journal of the American Academy of Dermatology
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J. Am. Acad. Dermatol. · Mar 2018
ReviewLangerhans cell histiocytosis: A neoplastic disorder driven by Ras-ERK pathway mutations.
Langerhans cell histiocytosis (LCH) is a disorder of myeloid neoplasia of dendritic cells that affects 1 in 200,000 children <15 years of age and even fewer adults. LCH presents with a spectrum of clinical manifestations. High-risk stratification is reserved for infiltration of blood, spleen, liver, and lungs. ⋯ Increased levels of phospho-ERK in lesional tissue, activation of Ras/Raf/MEK/ERK signaling with these mutations in vitro, and the mutual exclusivity of these mutations in a given patient suggest a central role for activation of the Ras/Raf/MEK/ERK oncogenic pathway in LCH. Immunohistochemical assessment of lesional tissue using the VE1 BRAFV600E mutation-specific antibody can serve as a screening tool for BRAFV600E-positive LCH. Case reports suggest that BRAFV600E-positive LCH unresponsive to standard therapy might respond to B-Raf-MEK pathway inhibition, but rigorous randomized clinical trials have yet to be performed.